Optimizing the Anticancer Effect of Doxil Using Pharmacokinetic and Pharmacodynamic Modelling

Abstract

Liposomal Dox, Doxil, enhances the antitumor effect of Doxorubicin by increasing its delivery ability to tumors. Therefore, quantitative studies on the relationship between the antitumor effect and liposomal characteristics will help to optimize the clinical application of Doxil in cancer treatment. Herein, we develop a physiological model to compute the pharmacokinetics and pharmacodynamics of Doxil, to calculate the time course of free Dox in the tumor space and linked this with a cell-killing kinetic model to quantify its anticancer effect. In this research, the two models utilize parametric figures of drug transportation in anatomical compartments, including plasma, capillary, interstitial, and tumor cells, to simulate the relationships between intravenously injected Dox and Doxil. Furthermore, simulations are performed to discuss the relationship between the anticancer effect and physicochemical properties, by comparing pharmacological parameters of Doxil.